Dr. Warren Manning has been selected for career initiation support by the Research Development Core of the proposed Harvard GRTC for his proposal entitled "Myocardial response to hemodynamic stress in aging". Dr. Manning is in Phase I of his career development as a new recruit into the Physician Scientist Training Program and proposes utilizing support from the GRTC to apply the techniques he has already developed to date. This will lead to an early entry into Phase II, or the more independent phase of his research career development. This supplementary support is thus aimed to enhance the primary direction of his research. Three years of work is outlined, to elucidate the mechanisms which underlay the age- associated decline in the cardiac hypertrophic response to pressure and volume overload. Dr. Manning will work directly with Dr. Wei, Principal Investigator of the Harvard GRTC, and Acting Director of the Gerontology Division of the Beth Israel and Brigham and Women's Hospitals, examining the hypotheses that (1) there is a change with age in the time course of the left ventricular hypertrophic response, (2) the age-dependent shift in myosin heavy chains isoforms may be related to preferential death of individual cardiocytes expressing the alpha heavy chain isoform, (3) that there is a differential response of the elderly myocardium of androgens on the hypertrophic response of the myocardium. The proposed studies, conducted in Dr. Wei's laboratory will be supervised by Dr. Jeanne Wei, Associate Professor of Medicine at Harvard Medical School who has trained a series of research oriented geriatricians focussed on cardiovascular aspects of aging. The proposed studies will support from the Bioengineering Core, the Biostatistics Core and the Physiology Cores.